Corporate Banner
Satellite Banner
Genomics
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Genetic Mystery of Behcet's Disease Unfolds Along the Ancient Silk Road

Published: Monday, January 07, 2013
Last Updated: Monday, January 07, 2013
Bookmark and Share
NIH researchers identify new gene variants associated with risk for complex inflammatory syndrome.

Researchers have identified four new regions on the human genome associated with Behcet's disease, a painful and potentially dangerous condition found predominantly in people with ancestors along the Silk Road. For nearly 2,000 years, traders used this 4,000-mile network linking the Far East with Europe to exchange goods, culture and, in the case of the Silk Road disease, genes. National Institutes of Health researchers and their Turkish and Japanese collaborators published their findings in the Jan. 6, 2013, advance online issue of Nature Genetics.

Named for the Turkish physician who described it in 1937, Behcet’s (pronounced BET’-chets) disease is triggered by complex genetic and environmental factors, and causes inflammation of blood vessels in various parts of the body. Common symptoms include painful mouth and genital sores, and eye inflammation that can lead to blindness. In some cases, it can be life-threatening, affecting blood vessels in the brain, lungs, and other vital organs. About 1 in 250 people in Turkey have Behcet's disease; others with the disease are found largely in regions along the Silk Road.

Genetic factors are thought to play a role in susceptibility to Behcet's disease, with the human leukocyte antigen (HLA) B-51 gene region of the genome, accounting for about 20 percent of genetic risk for the disease. Researchers have been aware of the HLA B-51 association for about 40 years. Two years ago, the research team identified gene associations at two other specific chromosome locations, or loci.

"The current study represents an important advance because it dramatically broadens the spectrum of genetic loci associated with Behcet's disease," said Dan Kastner, M.D., Ph.D., scientific director of the Intramural Research Program at the National Human Genome Research Institute and senior author of the study. "These newly discovered genetic associations provide a link between Behcet’s disease and other more common illnesses, and thereby suggest new therapies for Behcet’s disease. In addition, two of the newly discovered genes provide an intriguing link between genes and the microbes in our environment."

Researchers conducted a genome-wide association study (GWAS) that enrolled 1,209 Turkish people affected by Behcet's disease and 1,278 unaffected Turkish people — all residents of the country. They looked at many points on the human genome called single-nucleotide polymorphisms (SNPs), with each SNP representing a difference in a single DNA building block, called a nucleotide. Researchers then compared SNP differences between people with and without disease.

From nearly 800,000 SNPs, researchers detected and mapped a small number that are found in those who have Behcet’s disease at a significantly higher rate than in those without the disease, suggesting that the variant or another one nearby contributes to the disease.

"Each of the genetic factors may contribute a little to the overall risk of disease," said Elaine F. Remmers, Ph.D., staff scientist in NHGRI’s Inflammatory Disease Section and study co-author. "We are also identifying them in pathways that are important in inflammatory disease development."

She noted that not all of the 800,000 gene variants analyzed were directly genotyped. Genotyping involves examining a person's DNA at a site where a variation is commonly known to occur. Instead, the team used the strategy of imputing, or surmising, that there were genotypes worth investigating near known variants.

"That worked very well for us," Dr. Remmers said. "We found that our predicted genotypes were pretty good and that the associations we found were quite similar in both the predicted and the experimentally confirmed genotypes."

Each of the four newly identified gene regions is already known to play a role in immune regulation. The genetic associations have helped classify Behcet’s disease with more common inflammatory conditions such as psoriasis, inflammatory bowel disease and a form of spinal arthritis called ankylosing spondylitis.

Among the newly identified regions, researchers found:

•    An important association between Behcet’s disease and a gene called ERAP1. ERAP1 codes for a molecule that processes microbial proteins in white blood cells. Variants of this protein can lead to more or less efficient processing of microbial proteins before they are loaded onto HLA molecules for presentation to the immune system. The variants of ERAP1 identified in this study increase the risk of Behcet's disease, but only in those individuals with one specific HLA type, HLA-B51, which has previously been associated with Behcet’s disease. Dr. Kastner speculates that the ERAP1 variant associated with Behcet’s disease processes microbial proteins in such a way that they can be loaded onto the HLA-B51 molecule to trigger an abnormal immune response. The very same variant of ERAP1 that is associated with Behcet's disease is protective for ankylosing spondylitis and psoriasis, but only in people with the HLA types associated with those diseases.
•    A significant association of Behcet's disease with variants near the CCR1 gene. Proteins coded by this gene help infection-fighting blood cells migrate to sites of invading microorganisms. When this function is defective, the microorganisms can trigger a persistent inflammatory response.
•    An association of the disease with variants in the KLRC4 gene. The function of the receptor protein coded by this gene is not well understood, but the researchers suggest that it may be important to investigate further because it is located within the genomic region with the strongest evidence for linkage to a disease gene in a study of Turkish family health histories in which members sometimes have a rare familial form of Behcet’s disease.
•    An association with the STAT4 gene, in which different variants in the same vicinity of the genome increase risk for autoimmune diseases, including rheumatoid arthritis and lupus.

"We are incredibly excited about these latest findings," Dr. Kastner said. "Combined with our studies two years ago, the current genetic data make a strong case for a causal connection between Behcet’s disease and disorders such as ankylosing spondylitis, psoriasis, and inflammatory bowel disease. This raises real hope that some of the treatments that have been found effective in these other illnesses will have some utility in Behcet’s disease, thereby helping to alleviate suffering and prevent mortality."


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,100+ scientific posters on ePosters
  • More than 4,500+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Drug Might Help Treat Sepsis
A DNA enzyme called Top1 plays a key role in turning on genes that cause inflammation in mouse and human cells in response to pathogens. A drug blocking this enzyme rescued mice from lethal inflammatory responses, suggesting a potential treatment for sepsis.
Wednesday, May 18, 2016
NIH Funds New Studies on Ethical, Legal and Social Impact of Genomic Information
Four new grants from the National Institutes of Health will support research on the ethical, legal and social questions raised by advances in genomics research and the increasing availability of genomic information.
Wednesday, May 18, 2016
Researchers Identify Genetic Links to Educational Attainment
Researchers at NIH have suggested that the large genetics analyses may be able to help discover biological pathways as well.
Thursday, May 12, 2016
Submissions Open for the Cancer Moonshot Program
NCI opens online platform to submit ideas about research for Cancer Moonshot.
Tuesday, April 19, 2016
NIH Sequences Genome of a Fungus
Researchers at the Institute have sequenced genome of human, mouse and rat Pneumocystis that cause life-threatening Pneumonia in immunosuppressed hosts.
Tuesday, April 12, 2016
Decoding Ties Between Vascular Disease, Alzheimer’s
NIH consortium uses big data, team science to uncover complex interplay of factors.
Tuesday, March 15, 2016
Researchers Find Link Between Death of Tumor-Support Cells and Cancer Metastasis
Researchers at NIH have found that the lifespan of supportive cells in a tumor may control the spread of cancer.
Tuesday, February 23, 2016
Tick Genome Reveals Secrets of a Successful Bloodsucker
NIH-funded study could lead to new tick control methods.
Tuesday, February 09, 2016
Genomic Signature Shared by Five Types of Cancer
National Institutes of Health researchers have identified a striking signature in tumor DNA that occurs in five different types of cancer.
Monday, February 08, 2016
Cancer Drug Target Visualized at Atomic Resolution
New study using cryo-electron microscopy shows how potential drugs could inhibit cancer.
Thursday, February 04, 2016
Genome-Wide Study Yields Markers of Lithium Response
An international consortium of scientists has identified a stretch of chromosome that is associated with responsiveness to the mood-stabilizing medication lithium among patients with bipolar disorder.
Monday, February 01, 2016
Schizophrenia’s Strongest Known Genetic Risk Deconstructed
Suspect gene may trigger runaway synaptic pruning during adolescence – NIH-funded study.
Thursday, January 28, 2016
NIH Genome Sequencing Program Targets the Genomic Bases of Common, Rare Disease
The National Institutes of Health will fund a set of genome sequencing and analysis centers whose research will focus on understanding the genomic bases of common and rare human diseases.
Friday, January 15, 2016
Three Glaucoma-Related Genes Discovered
NIH-funded genetics analysis of glaucoma is largest to date.
Tuesday, January 12, 2016
International Study Reveals New Genetic Clues to AMD
NIH-funded research provides framework for future studies of AMD biology, therapy.
Tuesday, December 22, 2015
Scientific News
Benchtop Automation Trends
Gain a better understanding of current interest in and future deployment of benchtop automated systems.
First Large-Scale Proteogenomic Study of Breast Cancer
The study offers understanding of potential therapeutic targets.
Fungi – A Promising Source Of Chemical Diversity
Moulds and plants share similar ways in alkaloid biosynthesis .
Great Migration and African-American Genomic Diversity
Study examines genetic data to analyze regional differences in ancestry.
Faster, More Efficient CRISPR Editing
UC Berkeley scientists have developed a quicker and more efficient method to alter the genes of mice with CRISPR-Cas9, simplifying a procedure growing in popularity because of the ease of using the new gene-editing tool.
New Tool Could Change How Infectious Diseases Are Diagnosed
Scientists at the University of Utah School of Medicine, ARUP Laboratories, and IDbyDNA, Inc., have developed ultra-fast, meta-genomics analysis software called Taxonomer that dramatically improves the accuracy and speed of pathogen detection.
Insight into Bacterial Resilience and Antibiotic Targets
Variant of CRISPR technology paired with computerized imaging reveals essential gene networks in bacteria.
Illuminating Hidden Gene Regulators
New super-resolution technique visualizes important role of short-lived enzyme clusters.
Genes That Increase Children's Risk Of Blood Infection Identified
A team led by Oxford University has identified genes that make certain children more susceptible to invasive bacterial infections by performing a large genome-wide association study in African children.
Poverty Marks a Gene, Predicting Depression
New study of high-risk teens reveals a biological pathway for depression.
Skyscraper Banner

SELECTBIO Market Reports
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,100+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,500+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!